Understanding of the mechanisms of human disease is expanding at an exponential rate and the NIH Roadmap is challenging scientists to transform this knowledge into tangible health benefits for people. As a result, teams of academic investigators are formulating therapeutic hypotheses and generating the tools with which to test them. This is creating a heed for individuals with interdisciplinary training in translational medicine and chemical biology. Experience at Vanderbilt has identified a mechanism for training graduate students and postdoctoral/fellows in which they are co-mentored by physician-scientists and chemical biologists. The current application formalizes this experience into a program that will provide integrative training in therapeutic discovery. Its goal is to train graduate students and postdoctoral/fellows in the critical steps of therapeutic discovery, including identifying an unmet medical need, considering the molecular basis of the relevant disease, framing a hypothesis for a novel therapeutic approach,- and generating the lead molecules with which to test the hypothesis. Students will be recruited into the program following their first year in graduate school and postdoctoral will be recruited directly into the program. All students and postdocs will take two courses, Foundations of Chemical Biology and Therapeutic Discovery, as well as seminars in chemical biology and clinical pharmacology. The Therapeutic Discovery.course will provide introductory training in drug discovery and describe case studies in the application of an integrative approach to the discovery of new therapeutic strategies and agents. Guest lecturers will participate in the course to highlight the latest advances in disease treatment from the perspective of the individuals who made them. A community of trainees will be developed by participation in a web-based dialog among teams in both core courses, a weekly journal club, a monthly working group, and an annual retreat. Trainees will organize a symposium of extramural speakers as part of the annual retreat. Trainees will be co-mentored by individuals with expertise in translational medicine and chemical biology and their progress will be closely monitored by the Scientific Advisory Committee of the Training Program. The quality of the training provided will be evaluated annually by both an Internal Advisory Committee and an External Advisory Committee. Substantial investments in faculty recruiting and infrastructure coupled with extensive interactions between the College of Arts and Science and the School of Medicine provides a rich environment for integrative training in therapeutic discovery at Vanderbilt.